ATE412761T1 - Methode um rekombinante proteine in cho zellen zu exprimieren - Google Patents
Methode um rekombinante proteine in cho zellen zu exprimierenInfo
- Publication number
- ATE412761T1 ATE412761T1 AT03765075T AT03765075T ATE412761T1 AT E412761 T1 ATE412761 T1 AT E412761T1 AT 03765075 T AT03765075 T AT 03765075T AT 03765075 T AT03765075 T AT 03765075T AT E412761 T1 ATE412761 T1 AT E412761T1
- Authority
- AT
- Austria
- Prior art keywords
- cho cells
- recombinant proteins
- express recombinant
- express
- enhancing
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/108—Plasmid DNA episomal vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0216648.6A GB0216648D0 (en) | 2002-07-18 | 2002-07-18 | Method of expressing recombinant protein in CHO cells |
PCT/EP2003/007946 WO2004009823A1 (en) | 2002-07-18 | 2003-07-21 | Method of expressing recombinant protein in cho cells |
Publications (1)
Publication Number | Publication Date |
---|---|
ATE412761T1 true ATE412761T1 (de) | 2008-11-15 |
Family
ID=9940670
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT03765075T ATE412761T1 (de) | 2002-07-18 | 2003-07-21 | Methode um rekombinante proteine in cho zellen zu exprimieren |
Country Status (14)
Country | Link |
---|---|
US (3) | US20060003405A1 (de) |
EP (1) | EP1525320B1 (de) |
CN (1) | CN1296486C (de) |
AT (1) | ATE412761T1 (de) |
AU (2) | AU2003251434B2 (de) |
CA (2) | CA2489016C (de) |
DE (1) | DE60324430D1 (de) |
DK (1) | DK1525320T3 (de) |
ES (1) | ES2314248T3 (de) |
GB (1) | GB0216648D0 (de) |
HK (1) | HK1081595A1 (de) |
PT (1) | PT1525320E (de) |
SI (1) | SI1525320T1 (de) |
WO (1) | WO2004009823A1 (de) |
Families Citing this family (82)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0216648D0 (en) * | 2002-07-18 | 2002-08-28 | Lonza Biologics Plc | Method of expressing recombinant protein in CHO cells |
GB0319451D0 (en) * | 2003-08-19 | 2003-09-17 | Lonza Biologics Plc | Tropolone assay |
KR100942849B1 (ko) | 2004-03-30 | 2010-02-17 | 글락소 그룹 리미티드 | 면역글로불린 |
TWI307630B (en) | 2004-07-01 | 2009-03-21 | Glaxo Group Ltd | Immunoglobulins |
WO2006111387A2 (en) * | 2005-04-22 | 2006-10-26 | Lonza Biologics Plc. | Mammalian expression vector comprising the mcmv promoter and first intron of hcmv major immediate early gene |
EP1915394B1 (de) * | 2005-05-20 | 2021-01-27 | Lonza Biologics plc. | Expression auf hohem niveau von rekombinantem antikörper in einer säugetier-wirtszelle |
US7462698B2 (en) | 2005-07-22 | 2008-12-09 | Y's Therapeutics Co., Ltd. | Anti-CD26 antibodies and methods of use thereof |
US9884899B2 (en) | 2007-07-06 | 2018-02-06 | Promedior, Inc. | Methods for treating fibrosis using CRP antagonists |
KR20190140090A (ko) | 2007-07-09 | 2019-12-18 | 제넨테크, 인크. | 폴리펩티드의 재조합 생산 동안의 디술피드 결합 환원의 방지 |
UY32341A (es) | 2008-12-19 | 2010-07-30 | Glaxo Group Ltd | Proteínas de unión antígeno novedosas |
JP5980508B2 (ja) | 2009-03-11 | 2016-08-31 | プロメディオール, インコーポレイテッド | 自己免疫障害に対する処置方法 |
ES2612922T3 (es) | 2009-03-11 | 2017-05-19 | Promedior Inc. | Métodos de tratamiento y diagnóstico para trastornos de hipersensibilidad |
UA110323C2 (en) | 2009-06-04 | 2015-12-25 | Promedior Inc | Derivative of serum amyloid p and their receipt and application |
CA2765394C (en) | 2009-06-17 | 2020-08-18 | Promedior, Inc. | Sap variants and their use |
SG10201901417UA (en) | 2009-08-11 | 2019-03-28 | Genentech Inc | Production of proteins in glutamine-free cell culture media |
WO2011080050A2 (en) | 2009-12-11 | 2011-07-07 | Novartis Ag | Binding molecules |
US8940303B2 (en) | 2010-01-28 | 2015-01-27 | Glaxo Group Limited | CD127 binding proteins |
CN103037900B (zh) | 2010-02-24 | 2016-04-06 | 伊缪诺金公司 | 叶酸受体1抗体与免疫缀合物以及其用途 |
UA108227C2 (xx) | 2010-03-03 | 2015-04-10 | Антигензв'язуючий білок | |
AR080513A1 (es) | 2010-03-12 | 2012-04-11 | Inmunogen Inc | Moleculas de union cd37 y sus inmunoconjugados |
AR081556A1 (es) | 2010-06-03 | 2012-10-03 | Glaxo Group Ltd | Proteinas de union al antigeno humanizadas |
WO2012010635A1 (en) | 2010-07-22 | 2012-01-26 | Glaxosmithkline Biologicals S.A. | Novel antigen binding proteins |
WO2012019024A2 (en) | 2010-08-04 | 2012-02-09 | Immunogen, Inc. | Her3-binding molecules and immunoconjugates thereof |
EP3357511B1 (de) | 2011-06-30 | 2020-05-13 | Genzyme Corporation | Inhibitoren der t-zell-aktivierung |
US8802097B2 (en) | 2011-07-15 | 2014-08-12 | Oncomed Pharmaceuticals, Inc. | Anti-RSPO1 antibodies |
ES2657743T3 (es) | 2011-07-19 | 2018-03-06 | Philogen S.P.A. | Terapia secuencial con anti-CTLA-4 e IL-2 dirigida |
UY34317A (es) | 2011-09-12 | 2013-02-28 | Genzyme Corp | Anticuerpo antireceptor de célula T (alfa)/ß |
BR112014007035B1 (pt) | 2011-09-23 | 2021-05-04 | Oncomed Pharmaceuticals, Inc | anticorpos biespecíficos que se ligam a vegf/dll4, composição farmacêutica e célula procariótica, fúngica ou de levedura que compreende os mesmos, moléculas de polinucleotídeo, vetor, usos terapêuticos e método para a produção de um anticorpo |
BR112014012539B1 (pt) | 2011-11-23 | 2022-12-20 | Medimmune, Llc | Anticorpo que se liga especificamente a her3, composição compreendendo o mesmo, e usos do anticorpo |
MX2014014951A (es) | 2012-06-06 | 2015-03-13 | Oncomed Pharm Inc | Agentes aglutinantes que modulan la trayectoria hippo y sus usos. |
EP2674495A1 (de) * | 2012-06-14 | 2013-12-18 | Sanofi | CHO-Expressionssystem |
WO2014012007A2 (en) | 2012-07-13 | 2014-01-16 | Oncomed Pharmaceuticals, Inc. | Rspo3 binding agents and uses thereof |
RU2668824C2 (ru) | 2012-08-31 | 2018-10-02 | Иммьюноджен Инк. | Диагностические анализы и наборы для детекции фолатного рецептора 1 |
ES2540753T3 (es) | 2012-09-24 | 2015-07-13 | Lonza Biologics Plc. | Vectores de expresión que comprenden secuencias quiméricas de promotor y amplificador de citomegalovirus |
KR20150090919A (ko) | 2012-12-04 | 2015-08-06 | 온코메드 파마슈티칼스, 인크. | 결합제를 사용한 면역요법 |
WO2014100073A2 (en) * | 2012-12-21 | 2014-06-26 | Merck Sharp & Dohme Corp. | Expression vectors for recombinant protein production in mammalian cells |
BR112016003665B1 (pt) | 2013-08-30 | 2024-01-09 | Immunogen, Inc | Anticorpo ou fragmento de ligação ao antígeno do mesmo que se liga especificamente a um epítopo do receptor de folato 1, polinucleotídeo, vetor,célula hospedeira procariótica ou de levedura, composição, seus usos e métodos in vitro para detecção da expressão do receptor de folato 1 e identificação de um câncer |
US10203327B2 (en) | 2013-11-05 | 2019-02-12 | Novartis Ag | Organic compounds |
MX2016007066A (es) | 2013-12-02 | 2016-09-08 | Oncomed Pharm Inc | Identificacion de marcadores biologicos predictivos asociados con inhibidores de la via de wnt. |
ES2784238T3 (es) | 2014-02-02 | 2020-09-23 | Medimmune Ltd | Proteína quimérica compuesta por un dominio antagonista del NGF y un dominio antagonista del TNFalfa |
US8961992B1 (en) * | 2014-04-02 | 2015-02-24 | Tunitas Therapeutics, Inc. | Epsigam fusion protein |
CA2948275C (en) | 2014-04-08 | 2023-10-17 | Boston Pharmaceuticals Inc. | Binding molecules specific for il-21 and uses thereof |
JP2017512765A (ja) | 2014-04-11 | 2017-05-25 | メディミューン,エルエルシー | 二重特異性her2抗体 |
WO2015165480A1 (en) | 2014-04-30 | 2015-11-05 | Institute For Research In Biomedicine | Human cytomegalovirus vaccine compositions and method of producing the same |
BR112016027845A2 (pt) | 2014-05-29 | 2017-10-31 | Medimmune Llc | proteínas de fusão de ox40l e usos das mesmas |
AU2015289386A1 (en) | 2014-07-18 | 2017-03-09 | Celltheon Corporation | Methods and compositions for expression of polypeptides in a cell |
CN104195173B (zh) * | 2014-09-02 | 2017-03-08 | 北京比洋生物技术有限公司 | 具有双表达盒的谷氨酰胺合成酶高效表达载体 |
TW201619200A (zh) | 2014-10-10 | 2016-06-01 | 麥迪紐有限責任公司 | 人類化抗-ox40抗體及其用途 |
WO2016059602A2 (en) | 2014-10-16 | 2016-04-21 | Glaxo Group Limited | Methods of treating cancer and related compositions |
JP6755866B2 (ja) | 2014-11-10 | 2020-09-16 | メディミューン リミテッド | Cd73特異的結合分子及びその使用 |
GB2538120A (en) | 2014-11-11 | 2016-11-09 | Medimmune Ltd | Therapeutic combinations comprising anti-CD73 antibodies and uses thereof |
CN104561091A (zh) * | 2014-12-17 | 2015-04-29 | 华南理工大学 | 一种光学分析检测cho细胞增殖的方法及应用 |
CN105779501A (zh) * | 2014-12-26 | 2016-07-20 | 上海药明康德新药开发有限公司 | 运用cho宿主细胞进行重组蛋白的瞬时表达生产的方法 |
CN105802995A (zh) * | 2014-12-31 | 2016-07-27 | 上海复宏汉霖生物技术有限公司 | 一种利用cho细胞生产重组蛋白的基因表达***及真核表达载体 |
CN107206079A (zh) | 2015-01-09 | 2017-09-26 | 免疫医疗有限责任公司 | 检测人dpp‑4的测定法 |
WO2016178167A1 (en) | 2015-05-04 | 2016-11-10 | Vcn Biosciences Sl | Oncolytic adenoviruses with mutations in immunodominant adenovirus epitopes and their use in cancer treatment |
SI3313884T1 (sl) | 2015-06-29 | 2021-04-30 | Immunogen, Inc. | Protitelesa proti CD123 ter njihovi konjugati in derivati |
BR112018002039A2 (pt) | 2015-08-12 | 2018-09-18 | Medimmune Ltd | proteínas de fusão gitrl e usos das mesmas |
AU2016326609B2 (en) | 2015-09-23 | 2023-03-09 | Mereo Biopharma 5, Inc. | Methods and compositions for treatment of cancer |
IL309289A (en) | 2015-10-09 | 2024-02-01 | Genzyme Corp | Improved combustion technology (flow cytometry that reduces the expression of the reporter) for rapid sorting of substances in high masses |
SI3374398T1 (sl) | 2015-11-10 | 2020-07-31 | Medimmune, Llc | Vezavne molekule, specifične za ASCT2 in njihove uporabe |
EP3426680A4 (de) | 2016-03-10 | 2020-03-11 | Acceleron Pharma Inc. | Activin-typ-2-rezeptor-bindende proteine und verwendungen davon |
JP7116685B2 (ja) | 2016-04-15 | 2022-08-10 | エイチ. ルンドベック アー/エス | ヒト化抗pacap抗体及びそれらの使用 |
KR20220119529A (ko) | 2016-06-02 | 2022-08-29 | 애브비 인코포레이티드 | 글루코코르티코이드 수용체 작용제 및 이의 면역접합체 |
US20180119192A1 (en) | 2016-10-07 | 2018-05-03 | Genzyme Corporation | Early post-transfection isolation of cells (epic) for biologics production |
WO2018071345A1 (en) | 2016-10-11 | 2018-04-19 | Integrated Biotherapeutics, Inc. | Broadly neutralizing antibody targeting the ebolavirus glycoprotein internal fusion loop |
CR20190297A (es) | 2016-11-23 | 2019-11-01 | Bioverativ Therapeutics Inc | Anticuerpos biespecíficos que se unen al factor de coagulación ix y al factor de coagulación x |
CN107973841B (zh) * | 2016-12-23 | 2022-03-25 | 浙江海隆生物科技有限公司 | Cho细胞表达的重组牛病毒性腹泻病毒e2蛋白及亚单位疫苗的制备方法和应用 |
EP3583121A1 (de) | 2017-02-17 | 2019-12-25 | Lonza Ltd | Mehrortsspezifische integrationszellen für schwer zu exprimierende proteine |
GB201703418D0 (en) | 2017-03-03 | 2017-04-19 | Ge Healthcare Bio Sciences Ab | Method for cell line development |
CN110785494B (zh) | 2017-06-16 | 2024-07-02 | 隆萨有限公司 | 用于生产生物制品的通用自调节哺乳动物细胞系平台 |
ES2877659T3 (es) | 2017-12-01 | 2021-11-17 | Abbvie Inc | Agonista del receptor de glucocorticoides y sus inmunoconjugados |
US11447551B2 (en) | 2018-12-28 | 2022-09-20 | Sparx Bioscience Limited | Binding molecules specific for claudin 18.2, compositions and methods thereof, for the treatment of cancer and other diseases |
MA55529A (fr) | 2019-04-03 | 2022-02-09 | Genzyme Corp | Polypeptides de liaison anti-alpha bêta tcr à fragmentation réduite |
WO2020257281A1 (en) | 2019-06-18 | 2020-12-24 | United Therapeutics Corporation | Mitochondrial treatment of organs for transplantation |
CN113005140B (zh) * | 2019-12-19 | 2024-03-15 | 鲁南制药集团股份有限公司 | 一种具有双表达盒的gs表达载体及其应用 |
EP4186526A1 (de) | 2020-06-08 | 2023-05-31 | Y'S AC Co., Ltd. | Mittel zur umkehrung der resistenz gegen antikrebsmittel |
BR112023004840A2 (pt) | 2020-09-28 | 2023-04-18 | Medimmune Ltd | Compostos e métodos para tratamento de dor |
JP2022184105A (ja) | 2021-05-31 | 2022-12-13 | ワイズ・エー・シー株式会社 | 抗cd26抗体と免疫チェックポイント阻害剤との併用療法 |
US11807685B2 (en) | 2021-08-05 | 2023-11-07 | The Uab Research Foundation | Anti-CD47 antibody and uses thereof |
WO2023064947A1 (en) | 2021-10-15 | 2023-04-20 | Regenxbio Inc. | Antibodies and methods of using thereof |
WO2024062074A1 (en) | 2022-09-21 | 2024-03-28 | Sanofi Biotechnology | Humanized anti-il-1r3 antibody and methods of use |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2944850A1 (de) * | 1979-11-07 | 1981-05-27 | Bayer Ag, 5090 Leverkusen | Mittel zur regulierung des pflanzenwachstums, deren herstellung und deren verwendung |
US4963481A (en) * | 1985-12-18 | 1990-10-16 | Genetics Institute Inc | Promoter system |
US4968615A (en) * | 1985-12-18 | 1990-11-06 | Ciba-Geigy Corporation | Deoxyribonucleic acid segment from a virus |
GB8601597D0 (en) * | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
US5891693A (en) * | 1990-01-25 | 1999-04-06 | Alusuisse Holdings A.G. | Recombinant DNA methods vectors and host cells |
IT1262545B (it) | 1993-10-25 | 1996-07-02 | Menarini Ricerche Sud S P A A | Sistema di espressione per linee cellulari eucariotiche |
CA2177959C (en) * | 1993-12-23 | 2007-02-13 | Gregory Franklin Hollis | Homologous recombination antibody expression system for murine cells |
US5792651A (en) * | 1994-02-07 | 1998-08-11 | Qiagen Gmbh | Enhancement of the transfection efficiency of nucleic acids by using isopropanol in aqueous solutions |
GB0216648D0 (en) * | 2002-07-18 | 2002-08-28 | Lonza Biologics Plc | Method of expressing recombinant protein in CHO cells |
CN100429315C (zh) | 2003-03-11 | 2008-10-29 | 雪兰诺实验室有限公司 | 含有mcmv ie2启动子的表达载体 |
-
2002
- 2002-07-18 GB GBGB0216648.6A patent/GB0216648D0/en not_active Ceased
-
2003
- 2003-07-21 EP EP03765075A patent/EP1525320B1/de not_active Expired - Lifetime
- 2003-07-21 US US10/521,768 patent/US20060003405A1/en not_active Abandoned
- 2003-07-21 PT PT03765075T patent/PT1525320E/pt unknown
- 2003-07-21 DE DE60324430T patent/DE60324430D1/de not_active Expired - Lifetime
- 2003-07-21 CA CA2489016A patent/CA2489016C/en not_active Expired - Lifetime
- 2003-07-21 WO PCT/EP2003/007946 patent/WO2004009823A1/en active Application Filing
- 2003-07-21 AU AU2003251434A patent/AU2003251434B2/en not_active Expired
- 2003-07-21 CA CA2672809A patent/CA2672809C/en not_active Expired - Lifetime
- 2003-07-21 CN CNB038169142A patent/CN1296486C/zh not_active Expired - Lifetime
- 2003-07-21 DK DK03765075T patent/DK1525320T3/da active
- 2003-07-21 SI SI200331477T patent/SI1525320T1/sl unknown
- 2003-07-21 ES ES03765075T patent/ES2314248T3/es not_active Expired - Lifetime
- 2003-07-21 AT AT03765075T patent/ATE412761T1/de active
-
2006
- 2006-02-10 HK HK06101786A patent/HK1081595A1/xx not_active IP Right Cessation
-
2007
- 2007-12-21 US US11/962,261 patent/US7932087B2/en not_active Expired - Lifetime
-
2009
- 2009-02-19 AU AU2009200665A patent/AU2009200665B2/en not_active Expired
-
2010
- 2010-12-10 US US12/964,918 patent/US20110104745A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
US20110104745A1 (en) | 2011-05-05 |
AU2009200665B2 (en) | 2012-08-16 |
PT1525320E (pt) | 2009-01-23 |
SI1525320T1 (sl) | 2009-02-28 |
US7932087B2 (en) | 2011-04-26 |
CA2489016C (en) | 2012-01-17 |
CN1296486C (zh) | 2007-01-24 |
AU2003251434B2 (en) | 2009-03-05 |
DK1525320T3 (da) | 2009-02-23 |
WO2004009823A1 (en) | 2004-01-29 |
CA2672809C (en) | 2013-01-08 |
GB0216648D0 (en) | 2002-08-28 |
AU2009200665A1 (en) | 2009-03-12 |
CA2489016A1 (en) | 2004-01-29 |
US20060003405A1 (en) | 2006-01-05 |
CA2672809A1 (en) | 2004-01-29 |
DE60324430D1 (de) | 2008-12-11 |
ES2314248T3 (es) | 2009-03-16 |
EP1525320B1 (de) | 2008-10-29 |
HK1081595A1 (en) | 2006-05-19 |
EP1525320A1 (de) | 2005-04-27 |
US20080138902A1 (en) | 2008-06-12 |
CN1668749A (zh) | 2005-09-14 |
AU2003251434A1 (en) | 2004-02-09 |
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